Investigations of the mechanism of leukocyte interaction with chemotactic factors have included demonstration of the requirement of calcium and magnesium for leukocyte migration. Shifts in intracellular calcium by the calcium ionophore A23187 suggested calcium is important in modulating cyclic nucleotide metabolism. Levamisole increased neutrophil and monocyte in association with increases in cGMP. Four patients with defective leukocyte chemotaxis, high IgE recurrent pyogenic infections were given levamisole and in each case significant improvement of in vitro chemotaxis was demonstrated after in vivo levamisole. In related studies specific orientation of neutrophil centrioles, microtubules and submembranous microfilaments was demonstrated during chemotaxis. Migration requires microfilaments whereas direction appears dependent on microtubule assembly. In addition PMN granules orient in the leading front of migrating PMNs. In related studies a preferential release of specific granules during migration in vitro and exudation in vivo was demonstrated. The mechanisms of modulating the recruitment of leukocytes at inflammatory-immune sites is being actively studied in leukocytes obtained from normal subjects and patients with defective leukocyte migration.